dose-finding of pb-119 administered subcutaneously once weekly versus placebo in subjects with type 2 diabetes

Conditions: Type 2 Diabetes Mellitus (T2DM)

Summary: a phase 2, multicenter study to evaluate the efficacy and safety of twelve once weekly subcutaneous doses of pb-119 to patients with type 2 diabetes mellitus (t2dm) not well-controlled by metformin mono therapy.

this is a multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort, multiple dose study to evaluate the efficacy, safety, and tolerability of different doses of pb-119 to patients with t2dm not well-controlled by metformin monotherapy. patients will be assessed for eligibility over a 2 week screening period prior to a 4-week run-in period and a 12-week double-blind treatment period.a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort study to evaluate the efficacy and safety of twelve once weekly subcutaneous doses of pb-119 to patients with type 2 diabetes mellitus (t2dm) not well-controlled by metformin monotherapy the eligible patients will be randomized to 1 of 3 dose cohorts (a, b, or c). each patient will subsequently be randomized within the designated cohort to 1) active drug or placebo at a 3:1 active drug:placebo ratio and 2) exclusion from or inclusion in the pharmacokinetic (pk) blood sample collection subgroup at a 3:1 excluded:included ratio

Eligibility criteria:
inclusion criteria: 1. patients in whom t2dm has been diagnosed according to 2018 american diabetes association t2dm diagnostic criteria, have made lifestyle modifications (ie, diet and exercise) for at least 3 months prior to screening, and have been taking metformin for at least 3 months before screening with a stable dosage for at least 8 weeks (stable dosage is defined as metformin dosage ≥1500 mg/day or maximum tolerated dose). 2. males and/or females between the ages of ≥18 and ≤70 years at screening 3. hba1c ≥7.5% and ≤11% at screening and at week -1, visit 3.1; 4. fpg ≥126 and ≤240 mg/dl (≥7.0 and ≤13.3 mmol/l) at screening and at week -1, visit 3.1; 5. body mass index (bmi) ≥18.5 and ≤40.0 kg/m2 at screening, with inclusion of patients with bmis at the lower end of the range enrolled into the study to enable comparisons across bmi range; exclusion criteria: 1. medical history or current diagnosis of: 1. type 1 diabetes mellitus, diabetes caused by pancreas injury or by other diseases (like acromegaly or cushing syndrome); 2. diabetes acute complication, like ketoacidosis or hyperosmolar coma; 3. diagnosed proliferative retinopathy; 4. 3 instances of severe hypoglycemia (events during which the patient required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions; episodes may be associated with sufficient neuroglycopenia to have induced seizure or coma) in the 6 months prior to screening; 5. significant vascular disease; 2. current/ongoing diagnosis of any type of malignant tumor or evidence of recurrence in the 6 months prior to screening (patients who have been stable for ≥6 months or those who have had basal or squamous cell skin cancers removed and have no evidence of recurrence will not be excluded). patients with a medical history of any other type of cancer in the last 5 years prior to screening will be excluded; 3. severe cardiovascular diseases occurring within 6 months prior to screening (eg, congestive heart disease, myocardial infarction, acute coronary syndrome, apoplexy, transient ischemic attack);